Early RE-initiation of semaglutide after metabolic and bariatric surgery in youth: a randomized clinical trial - youth with severe obesity are less likely to reach, and maintain, body mass index (BMI)…

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Children's Hospital Los Angeles $884,146 on June 5, 2026, to conduct a randomized clinical trial examining early re-initiation of semaglutide after metabolic and bariatric surgery in obese youth.

The trial will enroll 80 youth ages 12–18 years with class III obesity who received semaglutide preoperatively and underwent metabolic and bariatric surgery. Participants will be randomly assigned to either early reintroduction of semaglutide two weeks postoperatively plus lifestyle modification (MBS + semaglutide arm) or metabolic and bariatric surgery alone with intensive lifestyle modification counseling per standard of care (MBS alone arm). The study addresses a gap in evidence-based guidelines for incorporating obesity pharmacotherapy after bariatric surgery in youth, targeting improved weight trajectories by addressing appetite and satiety mechanisms postoperatively. Recent research indicates that lower post-surgical glucagon-like peptide-1 levels and increased reward-based eating behaviors contribute to suboptimal early weight loss and weight regain; the trial will assess whether adding a GLP-1 receptor agonist early in the postoperative course improves outcomes.

Assessments will be conducted over a 24-month period. The award is funded under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), which supports extramural basic and clinical research improving understanding of mechanisms underlying disease and leading to improved prevention, diagnosis, and treatment of diabetes, digestive, and kidney diseases.

Performance occurs in Los Angeles, California, with a completion date of April 30, 2031.

Early RE-initiation of semaglutide after metabolic and bariatric surgery in youth: a randomized clinical trial - youth with severe obesity are less likely to reach, and maintain, body mass index (BMI) reduction with lifestyle modification and obesity pharmacotherapy alone.1-5 metabolic and bariatric surgery (MBS) remains the most effective intervention for managing severe pediatric obesity.6 up to one in four youth do not respond to MBS, whereas others experience weight regain.7 until recently, few alternative options existed for these young people other than another technique of MBS.4,5 recent research highlights that lower post-surgical levels of glucagon- like peptide-1 (GLP-1) and increased reward-based eating behaviors contribute to suboptimal early weight loss and weight gain reoccurence.8-11 a multi-pronged approach, immediately postoperatively, that adds GLP-1 receptor agonists (GLP-1RA), like semaglutide, to lifestyle modification may improve weight trajectories by targeting appetite and satiety mechanisms early in the postoperative course, yet this has never been tested in youth.2,12,13 to date, there are no standard of care guidelines for how to incorporate obesity pharmacotherapy after MBS in youth. Accordingly, this study aims to address this GAP in evidence-based guidelines involving early RE-initiation of semaglutide in youth, who have undergone MBS. Based on novel data from our pediatric MBS PROGRAM14, we have designed a 24-month randomized controlled trial involving 80 youth, ages 12-18 years, with class III obesity, who have been on semaglutide preoperatively and are undergoing MBS. Youth will be randomly assigned to (1) early reintroduction of semaglutide (MBS + semaglutide) two-weeks postoperatively or (2) MBS alone with no semaglutide. All participants will receive intensive lifestyle modification counseling per standard of care guidelines throughout the trial period.15,16 assessments will be conducted over a 24-month period to capture changes in anthropometric, cardiometabolic, and food intake outcomes. Aim 1: evaluate the efficacy of early RE-initiation of semaglutide immediately after MBS on weight reduction and body composition. H1: we hypothesize that early semaglutide RE-initiation is associated with significantly greater weight loss and reduction in FAT mass compared to MBS alone. Aim 2: examine the efficacy of early semaglutide RE-initiation immediately after MBS on GLP-1 and glucose profiles following a frequently sampled oral glucose tolerance test. H2: we hypothesize that early semaglutide RE-initiation will increase modified percent time in glucose range, captured with continuous glucose monitoring and increase stimulated GLP-1 levels compared to MBS alone. Aim 3: assess the effect of early semaglutide RE-initiation after MBS on objective measures of ad libitum food intake and food reinforcement using validated, experimental procedures (eating in the absence of hunger, palatable buffet meal, and relative reinforcing value of food task). H3: compared to MBS alone, youth who receive early semaglutide RE-initiation will decrease ad libitum food intake and decrease food motivation. This study will generate the first RCT evidence to inform early, phenotype-driven GLP-1RA use after adolescent MBS- advancing urgently needed, evidence-based protocols with direct implications for clinical practice. 1